Karolinska Institutet, Institute of Microbiology, Tumor and Cell Biology (KI/MTC)

KI/MTC focuses the research on immunology, infection biology and cell and tumor biology. The research interests are centered on the genetics and molecular biology of virus, bacteria and parasite replication, the role of gene products in abnormal cell growth, the use of microbes as probes for the study of signal transduction, transcription, translation, cell cycle regulation, cell differentiation, and cell death. Specific research areas include the biochemical mechanisms of cell growth control, transformation, signal transduction, and transcriptional regulation, the molecular genetics, molecular biology and molecular pathogenesis of latent, persistent and cytolytic infections, the characterization of receptor interactions and the mechanisms of cell entry, the interaction with cells involved in innate and adaptive immune responses, the pathogenesis of infection and rational drug design. Research at MTC is carried out in several scientific areas, this generates a diversified environment where cross-fertilization between different fields has the potential to generate novel and groundbreaking concepts.

Specific area in focus with the current proposal is Cancer, and Tumor Biology. It consolidates the research on the basic mechanisms causing tumors and tumor progression, host responses to tumor, genetic factors predisposing to or on contrary preventing development, protein products of these factors, such as oncogenes, cell cycle regulating genes, signal transduction genes, growth factors, apoptosis and cell aging controls, and suppressor genes and susceptibility genes. This area also includes studies on genetic cancer susceptibility and familiar cancers, related molecular epidemiology, on the interplay between malignant and normal cells, cell adhesion, angiogenesis, metastasis formation, aspects on tumor regression, and research on the relationship between infections and tumor development, as well as related bioinformatics and biom complexity. The application of this knowledge in the development on experimental treatments, such as gene and immunotherapy, and preventive measures is also included in this area of research.

MTC offers several levels of education. Today MTC offers Third cycle (doctoral) education programs in the research areas, including Immunobiology, Infection Biology, Cell Biology, Tumor Biology, Vascular biology, Infectious Diseases and Microbiology. It provides a dynamic research environment for approximately 100 or so postgraduate students engaged in many research activities. All students are registered for a PhD in Medical Science. Besides, MTC leads bachelor student education in Biomedicine including basic immunology covering morphology and general functions of the immune cells, proteins and organs of the immune system; maturation, interactions and regulation of innate and adaptive immune responses. It includes also clinically orientated immunology covering autoimmunity, allergy and transplantation immunology, morphology, taxonomy, genetics and metabolism of bacteria.

Current proposal is driven by a laboratory at MTC working on genetic vaccines against HIV and cancer. The laboratory conveys studies and educational activities in the field of the design, preclinical and clinical testing of DNA vaccines. Genetic vaccines have generated wide-spread interest for many applications, since DNA encoding a microbial or tumor-specific gene results in in vivo expression of the desired gene, protein production and presentation as an endogenous foreign antigen. The laboratory headed by Prof Wahren explores genetic vaccination against a protein abundant in human tumors, namely carcinoembryonic antigen (CEA). Studies were initiated in 2006. Preclinical evaluation results were published in 2007 (Hallermalm K et al. Pre-clinical evaluation of a CEA DNA prime/protein boost vaccination strategy against colorectal cancer. Scand J Immunol. 2007 Jul;66(1):43-51), and clinical trials were initiated in 2009. Active immunization approach was applied. Since then, the laboratory has tested two genetic CEA vaccines (wild type and mutated) and one glycoprotein vaccine in patients who are radically operated against colorectal cancer, with a primary surgical finding of Dukes B or C, diagnoses that confer around 50% risk for progression within 2-5 years. The CEA vaccines are tested in joint studies with H Mellstedt, Radiumhemmet, Karolinska Hospital, Stockholm. The laboratory also develops new tools for in vivo evaluation of passive-active vaccination efficiency.

In parallel, the laboratory has constructed HIV genes covering the highly variable sites of HIV envelopes and structural genes of Gag, subtypes A-E, the less variable parts of HIV regulatory genes and enzymes. This preparations were used as a prime, and recombinant vaccinia-based vector including subtypes A and E genes as a boost, to effectively activate innate, humoral, helper cell, and cytotoxic responses in humans, with memory retained up to over 3 years. Very high immunogenicity was demonstrated in a clinical phase 1 prophylactic studies. The laboratory performed phase 2 clinical studies in Tanzania, Mocambique, Sweden and a pediatric immunoprophylactic study in children in Italy.